Breast cancer is the most frequent malignancy in women, with over 202,000 new cases expected in 2002. While survival has improved, there remains a need for indicators that identify women at increased risk of treatment failure. In addition to disease characteristic features (e.g., stage, pathology), demographic and personal factors may also be associated with prognosis and treatment response. Among these, obesity has been implicated as a poor prognostic factor, although its magnitude is uncertain and the mechanisms by which it imparts poorer prognosis remain speculative. Obesity is also associated with risk of breast cancer and several other cancers. Obesity is prevalent in women with breast cancer, and is increasing in the United States and elsewhere. Thus, there is a need to understand the role of obesity in the totality of outcomes after breast cancer, including recurrence, risk of new cancers, and other health risks. Despite much previous research on breast cancer and obesity, many questions remain, and whether prospective interventions might improve prognosis and possibly reduce future cancer risk is unknown at this time. Using data from randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP), NCI sponsored Cooperative Group specializing in breast and colorectal cancers, we will investigate the significance of obesity in outcomes after early stage breast cancer. As a data source, clinical trials offer several advantages; uniform stage at diagnosis and detailed clinical/pathologic information, prescribed treatment plan with randomized assignment, and rigorous long-term follow-up with event-specific outcomes. Data from over 10,000 patients with follow-up from 7 to 15 years are available for use. Competing risks survival analysis will be the primary analytic tool. Specific project aims are to 1) determine the prognostic significance of obesity, accounting for menopausal status and tumor hormone receptors in order to address the predominant 'hormonal' hypothesis concerning obesity and prognosis, 2) determine the degree to which obesity increases risk for second primary cancers of the breast, endometrium, and other sites, and 3) determine whether obesity influences the benefits and risks of tamoxifen and cytotoxic chemotherapy. These investigations will provide valuable information for current patient management and insights into appropriate prospective interventions to improve breast cancer survivorship.